The term avermectin (previously referred to as C-076) is used to describe a series of compounds isolated from the fermentation broth of an avermectin producing strain of Streptomyces avermitilis and derivatives thereof. The morphological characteristics of the culture are completely described in U.S. Pat. No. 4,310,519. The avermectin compounds are a series of macrolides, each of which is substituted thereon at the 13-position with a 4'-(.alpha.-L-oleandrosyl)-.alpha.-L-oleandrose group. The avermectin compounds and the instant derivatives thereof have a very high degree of anthelmintic and anti-parasitic activity.
Also included are certain synthetically modified avermectins such as 22,23-dihydro avermectin B1a/B1b also known as ivermectin.
The avermectin series of compounds isolated from the fermentation broth have the following structure: ##STR1## wherein R is the 4'-(.alpha.-1-oleandrosyl)-.alpha.-1-oleandrose group of the structure: ##STR2## and wherein the broken line indicates a single or a double bond; R.sub.1 is hydroxy and is present only when said broken line indicates a single bond;
R.sub.2 is iso-propyl or sec-butyl; and PA1 R.sub.3 is methoxy or hydroxy. PA1 R.sub.1 is hydrogen or hydroxy provided that R.sub.1 is present only when the broken line at the 22,23-position indicates a single bond; PA1 R.sub.2 is iso-propyl or sec-butyl; PA1 R.sub.3 is hydroxy or methoxy; PA1 R.sub.4 hydroxy, .alpha.-L-oleandrosyloxy, or .alpha.-L-oleandrosyl-.alpha.-L-oleandrosyloxy, and the triangular figures at 8,9 and 14,15 indicate that there is present either a double bond or an epoxide, provided that at least one of the 8,9 and 14,15 prositions is an epoxide.
There are eight different major avermectin natural product compounds and they are given the designations A1a, A1b, A2a, A2b, B1a, B1b, and B2a based upon the structure of the individual compounds.
In the foregoing structural formula, the individual avermectin compounds are as set forth below. (The R group is 4'(.alpha.-L-oleandrosyl)-.alpha.-L-oleandrose):
______________________________________ R.sub.1 R.sub.2 R.sub.3 ______________________________________ Ala Double Bond sec-butyl --OCH.sub.3 Alb Double Bond iso-propyl --OCH.sub.3 A2a --OH sec-butyl --OCH.sub.3 A2B --OH iso-propyl --OCH.sub.3 Bla Double Bond sec-butyl --OH Blb Double Bond iso-propyl --OH B2a --OH sec-butyl --OH B2b --OH iso-propyl --OH ______________________________________
The avermectin compounds are generally isolated as mixtures of a and b components. Such compounds differ only in the nature of the R.sub.2 substituent and the minor structural differences have been found to have very little effect on the isolation procedures, chemical reactivity and biological activity of such compounds.